Time to treatment initiation in a retrospective cohort of patients with advanced lung cancer treated with an immune checkpoint inhibitor.
Authors: Alexander M. Quattlebaum, Andrew T. Faucheux, Greg B. Russell, Christopher Duckworth, John Hunting, Catherine A. Elko, Lara M. Khoury, Chance H. Bloomer, Jimmy Ruiz, Thomas William Lycan
Journal: Journal of Clinical Oncology (2023)

e21199 Background: Advanced lung cancer is diagnosed by imaging through screening, incidental findings, or during the workup of symptoms. Historically, there was no apparent benefit in expediting the times to biopsy, staging, and chemotherapy initiation. However, the widespread first-line use of immune checkpoint inhibitors (ICIs) can introduce delays such as biomarker testing and financial approval. We aimed to test whether the time to ICI treatment initiation was associated with worse clinical outcomes. Methods: We created a retrospective registry of all patients with advanced lung cancer who received at least one dose of an ICI for any first-line indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics and made a validated database. We defined the time to biopsy as the interval between the initial diagnostic imaging of the index cancer and the biopsy. We defined time to treatment initiation (TTI) as the interval between initial imaging and the first dose of ICI. Overall survival was the interval from the biopsy date to death. We used a Cox multivariate regression to model the continuous association of each additional month of TTI with survival. Confidence intervals (CI) were calculated to 95%, and p-values &lt; 0.05 were considered significant. The study had institutional IRB approval. Results: Our cohort consisted of 472 patients diagnosed with advanced lung cancer and treated with first-line ICI. The median time to biopsy was 15.5 days with an interquartile range (IQR) of 5-29 days, median TTI was 51 days (IQR 35-79), and median overall survival was 14.3 months (CI 11.5-16.6). TTI was not associated with survival by unadjusted or multivariate analysis (HR 0.98, CI 0.95-1.01 and HR 1.02, CI 1.00-1.05, respectively). Smoking history (HR 1.011, CI 1.00-1.02 per pack-year) and higher pre-treatment ECOG performance scores (p &lt; 0.01) were associated with worse survival. Tumor histologic subtype, autoimmune comorbidities, and toxic dust exposure were not associated with survival. The time to biopsy was not associated with survival by unadjusted or multivariate analysis (HR 0.97, CI 0.95-1.01, and HR 1.02, CI 0.97-1.07, for each additional week). Among the subset of patients with a symptomatic presentation of cancer (n = 363, 77%), longer TTI was associated with improved survival, but this effect became non-significant in multivariate analysis (HR 0.94, CI 0.89-0.99 and HR 0.96, CI 0.86-1.08, respectively). Conclusions: We did not find evidence that a shorter TTI is associated with improved survival among patients with advanced lung cancer starting first-line ICI. Additional studies are needed to test if baseline disease burden or other clinical factors can identify patients who would benefit from expedited initiation of treatment.